rs1141608

Variant names:

• chrX-149501018-G-A
• rs1141608
• ENST00000651111.1:c.-196C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-149501018-G-A
• chrX-149501018-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000651111.1(ENSG00000241489):​c.-196C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,165,083 control chromosomes in the GnomAD database, including 54,181 homozygotes. There are 119,286 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (4367 hom., 9370 hem., cov: 22)
  • Exomes 𝑓: 0.35 (49814 hom. 109916 hem.)
• Consequence: ENSG00000241489 ENST00000651111.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.771
• Publications: 22 publications found

Genes affected

ENSG00000241489 (HGNC:):

IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

IDS Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 2

  Inheritance: XL, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, PanelApp Australia, Myriad Women’s Health
• mucopolysaccharidosis type 2, attenuated form

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• mucopolysaccharidosis type 2, severe form

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-149501018-G-A is Benign according to our data. Variant chrX-149501018-G-A is described in ClinVar as Benign. ClinVar VariationId is 92619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651111.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDS	NM_000202.8	MANE Select	c.438C>T	p.Thr146Thr	synonymous	Exon 4 of 9	NP_000193.1
	IDS	NM_001166550.4		c.168C>T	p.Thr56Thr	synonymous	Exon 4 of 9	NP_001160022.1
	IDS	NM_006123.5		c.438C>T	p.Thr146Thr	synonymous	Exon 4 of 8	NP_006114.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000241489	ENST00000651111.1		c.-196C>T		5_prime_UTR_premature_start_codon_gain	Exon 9 of 14	ENSP00000498395.1
	IDS	ENST00000340855.11	TSL:1 MANE Select	c.438C>T	p.Thr146Thr	synonymous	Exon 4 of 9	ENSP00000339801.6
	IDS	ENST00000370441.8	TSL:1	c.438C>T	p.Thr146Thr	synonymous	Exon 4 of 8	ENSP00000359470.4

Frequencies

GnomAD3 genomes AF: 0.312 AC: 34181 AN: 109470 Hom.: 4371 Cov.: 22

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.00283

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.275 AC: 50217 AN: 182867 AF XY: 0.273

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.00115

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.347 AC: 366356 AN: 1055561 Hom.: 49814 Cov.: 25 AF XY: 0.328 AC XY: 109916 AN XY: 335471

African (AFR) AF: 0.245 AC: 6245 AN: 25485

American (AMR) AF: 0.165 AC: 5799 AN: 35161

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 6417 AN: 19114

East Asian (EAS) AF: 0.00110 AC: 33 AN: 30099

South Asian (SAS) AF: 0.0926 AC: 4960 AN: 53538

European-Finnish (FIN) AF: 0.318 AC: 12791 AN: 40285

Middle Eastern (MID) AF: 0.313 AC: 1269 AN: 4051

European-Non Finnish (NFE) AF: 0.392 AC: 314445 AN: 803062

Other (OTH) AF: 0.322 AC: 14397 AN: 44766

GnomAD4 genome AF: 0.312 AC: 34176 AN: 109522 Hom.: 4367 Cov.: 22 AF XY: 0.294 AC XY: 9370 AN XY: 31922

African (AFR) AF: 0.252 AC: 7550 AN: 30012

American (AMR) AF: 0.249 AC: 2576 AN: 10335

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 870 AN: 2626

East Asian (EAS) AF: 0.00283 AC: 10 AN: 3528

South Asian (SAS) AF: 0.0681 AC: 176 AN: 2585

European-Finnish (FIN) AF: 0.299 AC: 1689 AN: 5640

Middle Eastern (MID) AF: 0.420 AC: 89 AN: 212

European-Non Finnish (NFE) AF: 0.390 AC: 20464 AN: 52414

Other (OTH) AF: 0.319 AC: 478 AN: 1497

Alfa AF: 0.339 Hom.: 10442

Bravo AF: 0.308

EpiCase AF: 0.397

EpiControl AF: 0.393

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Mucopolysaccharidosis, MPS-II (4)
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.74
PhyloP100		0.77
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		0.0
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1141608; hg19: chrX-148582549; COSMIC: COSV61712415; COSMIC: COSV61712415;